There is a need to develop predictive tests of hormonal responsiveness in normal and neoplastic tissues. We have selected for these studies an estrogen target organ, the breast, and will investigate certain biochemical parameters which are thought to be indicators of hormonal responsiveness. These end points include the presence of specific estrogen binding capacity and activities of certain enzymes concerned with carbohydrate and lipid metabolism. These studies will be conducted on specimens of human and rodent mammary glands, with emphasis on human breast carcinomas and nonmalignant diseases of the breast. Investigation of these biochemical parameters in the mammary gland at various stages of differentiation, e.g., pregnancy, lactation, involution, will enable us to characterize the physiological spectrum of normal tissue and thereby enable us to identify similarities and deviations between normal and abnormal breast tissue. Studies in our laboratory have already demonstrated that human and rodent breast carcinomas exhibit differences in their respective biochemical properties compared to normal or nonmalignant breast tissues. Preliminary data indicate that clinical response to endocrine organ ablation may be correlated with the presence of estrogen receptors and enzymes profiles of the neoplasm. Extension and confirmation of these findings should lead to the development of a discriminant test for the hormonal responsiveness of malignant breast cancers, greatly enhancing the efficacy of a planned therapeutic regimen.